The translation of xenogeneic eukaryotic mRNA's has been previously studied in the undifferentiated frog oocyte system. Similar studies utilizing differentiated eukaryotic cells have been unsuccessful due to the inability of the employed methodologies to efficiently insert mRNA into cultured cells intact. This problem will be overcome by the sequestration of messenger RNA within large unilamellar liposomes. Such a procedure provides the dual advantage of protecting encapsulated message from external nuclease degradation and delivering the sequestered mRNA to a wide variety of cells by liposome-cell fusion. We have employed this technique to entrap rabbit globin mRNA and to deliver it to human Hep-2 cells in vitro. Insertion of message by this method induces the production of rabbit globin as assessed by SDS gel electrophoresis. This procedure can now be expanded to include a variety of messages and recipient cells. I plan to investigate the following: 1) Maximization of sequestration of high molecular weight RNA by liposomes and its subsequent transfer to cells in vitro. 2) Expansion of the globin mRNA-Hep-2 cell system to a variety of messages and cell types particularly those of the circulatory system. 3) Evaluation of the effect of mRNA origin and recipient cell type on the duration of translation, including: turnover of translation product, affinity of message for polysomes, and half-life of message. 4) Evaluation of the assembly of the translation products of messages coding for multisubunit complexes, both for noncatalytic (globin) and catalytic proteins (enzymes of the yeast galactose utilization pathway). Such an investigation will result in the development of techniques which will facilitate the study of translational control in differentiated mammalian cells and provide for a greater understanding of the factors involved in translation. Thus, if in the future, a way could be found of prolonging the life of message or stabilizing its genetic information, a feasible approach to the clinical treatment of genetic defects in the cells of the peripheral blood may be possible e.g., enzyme and immune deficiencies and sickle cell anemia.